Health

The DNA health checks that could lead to tailor-made treatments

Most of us consult our GP when we have a medical problem that needs urgent attention.

But could we soon be visiting the doctor to find out what illnesses are coming our way — in ten, 20 or even 30 years’ time — and what we can do to prevent them?

That’s the tantalising prospect raised by a groundbreaking NHS pilot project, involving around 1,000 patients in the North-East of England, which hopes to identify what ‘hidden’ threats to heart health might be lurking in patients’ DNA.

Genetic testing is already widely used to diagnose diseases caused by mutations or faults in a single gene — such as cystic fibrosis, an incurable illness where persistent lung infections make breathing increasingly difficult 

Blood samples from volunteers aged 40 and over will be analysed for genetic patterns that have been linked to a greater risk of having heart attacks and strokes later in life, even if they have no existing symptoms such as raised cholesterol or high blood pressure.

The idea is that doctors would then monitor them, give them advice on diet and lifestyle and even start them on preventative medication.

This approach is a form of ‘personalised’ medicine, matching treatment much more closely to an individual’s medical risk rather than that suggested solely by studies of large groups of patients of similar age, sex or ethnicity.

And it could reduce the chances of commonly used pills — such as cholesterol-lowering statins — being dished out to patients who may benefit little from them but who may then suffer unpleasant side-effects as a result.

Personalised medicine is already having an impact in cancer care, where treatment is moving away from treating patients with, for example, ‘breast cancer drugs’ or ‘prostate cancer drugs’ towards using drugs to better target the genetic anomaly of their cancer.

Blood samples from volunteers aged 40 and over will be analysed for genetic patterns that have been linked to a greater risk of having heart attacks and strokes later in life

Blood samples from volunteers aged 40 and over will be analysed for genetic patterns that have been linked to a greater risk of having heart attacks and strokes later in life

Some experts see the latest project as proof that, after years of promise, genetic research is finally starting to deliver benefits.

The company behind the pilot tests — which cost around £20 each — an Oxford University spin-out called Genomics plc, says it can use the same genetic sequencing methods to work out someone’s risk of 15 other conditions — from age-related macular degeneration (a common cause of blindness), breast cancer and lung disease to multiple sclerosis, prostate cancer and type 2 diabetes.

But is genetic analysis really going to benefit millions — or will it simply terrify many about problems they can do little about?

Genetic testing is already widely used to diagnose diseases caused by mutations or faults in a single gene — such as cystic fibrosis, an incurable illness where persistent lung infections make breathing increasingly difficult.

A much more complex task has been identifying the hundreds, in some cases thousands, of genes involved in common illnesses such as heart disease and type 2 diabetes.

To finesse this process, scientists have found a solution in what’s called ‘polygenic risk scores’.

Some patients, for example, may be able to come off statins if their genetic risk score for heart disease is extremely low and their cholesterol level is only just in the danger zone

Some patients, for example, may be able to come off statins if their genetic risk score for heart disease is extremely low and their cholesterol level is only just in the danger zone

This is where computer algorithms scan data on all the genes known to carry mutations that increase the risk of a certain disease and cross-reference those to an individual’s genes (based on blood test results) to work out a score for how likely someone is to develop that disease, compared with the general population.

For example, it may calculate that your genetic profile means your risk of heart disease is higher than 10 per cent of the population — a relatively low risk — or higher than 95 per cent of the population, a high risk.

GPs will add the genetic risk score to all the other data they use to work out a patient’s heart disease risk, such as age, sex, body mass index, smoking status, cholesterol and blood pressure.

‘It’s about coming up with a more accurate risk score,’ says Professor Sir Peter Donnelly, founder of Genomics Plc.

Some patients, for example, may be able to come off statins if their genetic risk score for heart disease is extremely low and their cholesterol level is only just in the danger zone.

There may be other benefits. A 2018 study in Finland involving more than 7,000 people found 90 per cent tried to make improvements to their health — such as quitting smoking or losing weight — after being confronted with their genetic risk of heart disease.

But not everyone is convinced genetic profiling is the panacea medicine has been waiting for.

Tim Spector, professor of genetic epidemiology at King’s College London and author of several books on how genes affect our health, says: ‘Polygenic risk scores may work very well for the five per cent of those who have all the genetic risk factors for a particular disease.

‘But it’s not going to be much help to the other 95 per cent.’

That’s because, the lower the polygenic risk score, the less influence genes are likely to have on disease outcome.

So a lower score does not mean someone is immune to an illness; just that genes are likely to play a much smaller part if they do get it, says Professor Spector.

‘The more you move away from that top five per cent who have strong genetic risk factors, the less useful this information becomes,’ he adds.

Professor Spector says the complexity of genetics research means that while it may be a valuable research tool it could have limited application in everyday medicine.

Even when scientists have managed to pinpoint the huge numbers of genes involved in disease risk, things don’t always fall into place as expected.

‘I’ve been involved in lots of studies on twins, and even when two people have identical genetic markers for heart disease it doesn’t necessarily mean they both die of it,’ he says.

‘With some illnesses, we run the risk of scaring patients. If someone has a high polygenic risk score for bowel cancer, we can do something about it [by advising changes to diet] but if it’s a high score for pancreatic cancer [which may be untreatable] it could be disastrous.’

Dr Stuart Hogarth, a lecturer in sociology of science and technology at Cambridge University, has been tracking the development of genetic risk scoring for more than a decade.

‘GPs already have very effective ways of measuring a patient’s chances of, for example, developing heart disease,’ he says.

‘If you shift to also testing genes, it will depend on which genes you analyse.

‘The fact is, some scientists are questioning whether genetics research is really proving as useful or informative as was first hoped.’

Patients’ genes being used to improve care

Genetic testing raises the possibility of healthy people finding out what diseases they are more likely to develop, from heart disease to cancer. 

With this information they can take steps — such as lifestyle changes or medical treatment — to reduce their risk.

It’s also being used in some patients already diagnosed with a condition to tailor their treatment to fit their genetic blueprint.

This ‘personalised medicine’ is being trialled by the NHS for stroke and heart attack risk, but there are other DNA tests already available on the NHS and privately.

For example, the BRCA gene test is used by the NHS to identify healthy women at increased risk of breast and ovarian cancer. The blood test can also be used to identify men at risk of prostate cancer, and is available to anyone with a family history of the disease.

Private companies offer genetic tests ‘screening’ for a range of diseases, including Parkinson’s and dementia, although the increased risk from having certain genes may be small

Private companies offer genetic tests ‘screening’ for a range of diseases, including Parkinson’s and dementia, although the increased risk from having certain genes may be small

Since the test was introduced more than 20 years ago, hundreds of thousands of women at higher risk of breast cancer have been identified. In some cases, they’ve chosen to have a preventative mastectomy — as Angelina Jolie did in 2013 after testing positive for faulty BRCA genes.

Genetic testing is also available to check for the risk of hypertrophic cardiomyopathy, a thickening of the heart muscle and a cause of sudden cardiac death and some heart rhythm problems. This screening is offered to those with a family history of the disease, but it’s not perfect because not all the relevant genes have been identified.

Other DNA tests available on the NHS include one for Huntington’s Disease, an inherited condition that affects the brain and nervous system. Private companies offer genetic tests ‘screening’ for a range of diseases, including Parkinson’s and dementia, although the increased risk from having certain genes may be small.

DNA tests can be used to predict disease progression, too. For instance, the Oncotype DX test predicts the chance of breast cancer recurring by looking at the activity of 21 key genes in cancer tissue (it is one of three tests, along with EndoPredict and Prosigna, used by the NHS).

Genetic testing is also useful when deciding how to treat cystic fibrosis and inflammatory bowel disease, by identifying how well the body metabolises a drug — or whether it will work at all.

Rachel Ellis 


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